A STUDY  OF  ISODEHYDROACETIC 

ESTER 


BY 


EUGENE  MILLER  McCOLM 


THESIS 

FOR  THE 


DEGREE  OF  BACHELOR  OF  SCIENCE 

IN 

CHEMICAL  ENGINEERING 


COLLEGE  OF  LIBERAL  ARTS  AND  SCIENCES 


UNIVERSITY  OF  ILLINOIS 


1922 


UNIVERSITY  OF  ILLINOIS 


_-Ma5L_25.-la22.192 

THIS  IS  TO  CERTIFY  THAT  THE  THESIS  PREPARED  UNDER  MY  SUPERVISION  BY 

Su  g_en  e_  _ -_1 1IL  er__  NGj^ol_m 

ENTITLED _4__STUDY_0F_XSpJDEHY2MQMXG_ESiIL^ 


IS  APPROVED  BY  ME  AS  FULFILLING  THIS  PART  OF  THE  REQUIREMENTS  FOR  THE 
DEGREE  OF  Bachelor  of  Science  in  Chemical  Engineering. 


Approved  : 


Instructor  in  Charge 


HEAD  OF  DEPARTMENT  OF 


500250 


Digitized  by  the  Internet  Archive 
in  2016 


https://archive.org/details/studyofisodehydrOOmcco 


ACKNOWLEDGMENT 

I wish  to  express  my  thanks  to  Dr*  B* 

L*  Souther,  under  whose  supervision 
this  work  was  done,  for  his  many  helpful 
suggestions* 


E*  M*  M 


, 

. 


TABLE  OP  COHTEHTS 


page 

I.  Literature 

A*  Preparation  of  the  Ester  1 

B*  Preparation  of  the  chlo*  ^-pyrones  4 

II*  Reactions  7 

III*  Experimental  Work 

A*  Preparation  of  the  acid  and  ester  9 

The  hydrochloric  acid  method  11 

B*  Chlorination  of  the  ester  12 

IV*  Summary  15 


. 
. 


. 


. 


. 


- 


. 


- 


. 


A STUBY  OP  ISODEHYDROACETIC 
ESTER 


LITERATURE 

A*  Preparation  of  the  Ester* 

An  tf-pyrone  is  a cyclic  compound  having  an  oxygen  atom  in  the  rinj: 
and  an  oxygen  atom  on  thS  carbon  atom*  It  has  the  follow- 
ing structure: - 

5 6 

CH  = CH 

4 CH  JTOi 

*CH  — CB 
3 2 

The  atoms  are  numbered  as  shown* 

Isodehydroacetio  aoid  is  the  dimethyl  cumalinic  acid  in 
which  the  methyl  groups  are  on  the  fourth  and  sixth  carbon 
atoms*  It  has  the  following  structure 

COOH 


/v 


3 -vv 


cH^-e 


:CCH 


CH  — CO 

The  ester  that  was  studied  was  the  ethyl  ester  of  this 

aoid* 

To  prepare  the  aoid  and  ester  the  following  method  was 
used1*  "According  to  Hantzsch  the  first  condensation  product 
is  formed  by  the  action  of  sulfuric  acid  on  aoetoaoetic  ester. 

It  crysatallizes  from  ether  in  compact  crystals,  and  from  water 
^ Liebig's  Annalen,  V*  259,  p*  151* 


, 

, 


« 


. 


E 

in  loose,  soft  crystals  resembling  asbestos.  In  both  cases 
it  is  pure  for  its  melting  point  is  not  changed  by  recrystallizl- 
ing  from  hot  water.  It  reacts,  after  freeing  from  solfnric 
aoid^  extreemly  acid.  It  breaks  up  in  alcoholic  potash  to  the  po- 
tassium salt  of  the  acid  ( isodehydroaoetio ) and  to  the  ethyl 
ester  of  this  acid. 

According  to  this  the  condensation  product  may  be  regarded 
as  an  ether  of  the  acid  and  ester.  After  the  breaking  up  of 
the  lactone  ring,  both  substances  are  thought  to  be  formed 
by  the  addition  of  two  molecules  of  water. 

To  prepare  the  ester  it  is  not  necessary  to  reorystallizt 
the  first  condensation  product,  nor  to  use  the  alcoholic  pot- 
ash. The  best  plan  is  to  dissolve  the  product,  after  filtra- 
tion, in  a solution  of  ether  and  chloroform  which  is  lighter 
than  water  to  allow  washing  with  ease.  This  solution  is  wash- 
ed with  water  several  times  to  remove  the  sulfuric  acid,  and 
is  then  shaken  with  a concentrated  solution  of  potash.  The 
potassium  salt  of  the  acid  will  be  found  in  the  potash  layer 
and  the  ester  will  be  in  the  ether-chloroform  layer.  The  acid 
is  recovered  merely  by  neutralizing  the  potash  with  hydro- 
chloric acid  when  the  isodehydroacetic  acid  will  be  precipitat- 
ed. The  ester  is  recovered  pure  by  diminished  pressure  dis- 
tillation of  the  ether  chloroform  solution. 

130  grams  of  the  acid,  and  190  grams  of  the  ester  were 
obtained  in  this  manner  from  a liter  of  acetoacetic  ester." 


* 


t 


3 


Thg  following  additions  were  made  to  the  above,1 2 

"The  sulfuric  acid  and  the  acetoaoetio  ester  must  be  mixed 
slowly  and  with  oooling,  and  allowed  to  stand  from  ten  to  four- 
teen days.  When  a little  of  this  solution  mixed  with  ioe  and 
water  gives  a heavy, turbid  precipitate,  the  solution  is  ready 
to  be  worked  up.  It  is  poured  intt  a mixture  of  ioe  and  water 
that  has  three  times  the  weight  of  the  solution  and  allowed 
to  stand  for  twentyfour  hours.  It  is  then  filtered." 

The  method  that  I used  was  a little  different  from  the 
a$ove • 

Another  method  for  the  preparation  of  the  ester  alone  is 

2 

by  the  use  of  hydrochloric  acid.  According  to  this  method 
acetoaoetio  ester  is  saturated  with  dry  hydrogen  chloride  at  the 
temperature  of  ice.  The  mixture  is  then  allowed  to  stand  for  & 
month  at  the  above  temperature  and  is  then  fractioned  under  di- 
minished pressure.  Hembd  obtained  a yield  of  420  gr%ms  of  iso- 
dehydroaoetic  ester  from  a kilo  of  acetoacetic  ester. 


1 Elbs,  II,  p.  248 

2 Beilstein,  I,  p.  776$  and  Hembd,  Thesis  at  Kiel,  Ger.,1914. 


» 


t 


r 


c 


4 


B.  Preparation  of  the  ohlor  d-pyrones. 

For  convenience  the  formula  of  the  simplest  of  the  ^-pyrones, 
mesityn,  is  given  again,  with  the  carbon  atoms  numbered  av  shown* 

5 6 

^CH^rCH 

4 CHn  > 1 

XCH — CO 
3 2 

Bland  and  Thorpe  give  the  following  preparations:-  1 
6-ohloro  d.-pyrone  is  obtained  when  glntaoonio  acid  is  treated  with 
acetyl  chloride  in  the  presence  of  phosphorous  trichloride.  The 
ohlor  pyrone  formed  has  the  following  formula 


CH 


.CH=CC1 

* > 

VCH  — CO 


6-chlor  4-methyl  ^-pyrone  is  formed  by  the  reaction  of  acetyl 
chloride  with  6-hydvozy  4-methyl  oc-pyrone. 


Genveresse2  gives  a method  for  the  chlorination  of  ispdehy- 
droacetlc  ester  (ethyl).  In  this  method  the  ester  is  cooled  to 
0°  and  the  equivalent  amount  of  sulfuryl  chloride  is  added  drop 
by  drop.  When  the  reaction  is  complete  crystals  of  the  chlor- 
inated ester  form  in  the  liquid.  These  are  dissolved  in  ether  and 
the  solvent  evaporated  in  a vacuum  over  sulfuric  acid.  If  this 
ohlor  ester  is  heated  with  hydrochloric  acid  in  a sealed  tube 
to  260° • oarbon  dioxide,  ethyl  acetate,  and  ohlormethyl  ether 

are  formed.  If  this  is  so  the  chlorine  wqs  present  on  one  of  the 
methyl  groups* 

^Jour.  Chem*  Soo*  101,  856-70  2Annales  de  Chimie  V.24,  ser*6fp*9 


5 


Oppenheim  and  Preoht^  have  another  method  for  the  prepara- 
tion of  the  above  ohlor  acid.  In  this  method  a mixture  of  ohlor- 
ine  in  chloroform  and  a chloroform  solution  of  isodehydro- 
aoetio  acid  are  allowed  to  stand  for  a half  hour*  The  ohlor 
acid  crystallizes  immediately  into  small  needles  that  are  solu- 
ble in  alcohol  and  melt  at  93°  C#  On  longer  standing^  six  hours 
or  more,  a syrupy  liquid  forms  *hioh  has  not  yet  been  identified. 

Peohmann  and  Mills2  give  a method  for  the  chlorination 
of  the  methyl  ester  of  oumalinic  acid.  To  prepare  this  chlor 
ester  a mixture  of  the  pure  ester  of  the  acid  is  allowed  to 
stand  with  a solution  of  chlorine  in  carbon  tetrachloride#  Afto* 
t#o  or  three  days  hydrochloric  acid  begins  to  come  off,  crystals 
form,  and  the  solution  bleachas  out#  When  free  chlorine  is  no 
longer  present  the  crystals  are  filtered  and  washed  with  ether# 
The  melting  point,  after  recrystallization  from  aloohol,  is 
134-136°  C. 

Feist3  gives  a method  for  the  chlorination  of  isodehydro- 
acetio  ester#  The  ohlor  ester  is  formed  by  the  reaction  of 
the  ester  with  sulfuryl  chloride  at  the  temperature  of  ice. 

Ether  is  used  as  the  solvent#  The  product  is  white  and  orystal- 
lineand  melts  at  57° • 

Thole  and  Thorpe4  give  methods  for  the  preparation  of  seven*- 


Berichte  V# 

9; 

P* 

1101. 

Ibid  V#  37, 

3831 

Annalen  Y# 

346, 

P« 

74# 

Jour#  Cheip# 

Soc 

• Y. 

99,  p.  2208 

* 


? 


6 


al  of  the  ohlor  ^-pyrones. 

6-chloro  3-methyl  ^-pyrone  is  prepared  by  boiling  methyl 
glutaeonio  aoid  with  acetyl  chloride.  Melting  point  71°  C. 

The  similar  ethyl  pyrone  ii  formed  in  the  same  manner  by 
treating  the  ethyl  glutaaonic  aoid  in  the  same  way.  It  has  a 
melting  point  of  39°  and  a boiling  point  of  133°. 

The  similar  benzyl  pyrone  is  formed  by  boiling  6-hydroxy 
3-benzyl  *-pyrone  with  acetyl  chloride.  It  has  a melting  point 
of  74°. 

6-ohloro  3;i4-dimethyl  ^-pyrone  is  formed  by  heating 
dimethyl  glntaconic  acid  with  two  moles  of  acetyl  chloride 
in  a sealed  tube  at  100°  for  ten  hours. 

The  ohlor  anhydride  of  the  trimethyl  glutaconio  aoid  cannot 
be  formed  in  the  same  manner. 

Peohmann  and  Mills1  have  a method  for  the  preparation  of 
ohlor  oumalinio  acid.  It  is  formed  by  the  action  of  chlorine 
in  an  acetic  acid  solution  of  the  aoid  in  the  presence  of  io- 
dine. It  has  the  following  structure *- 


This  structure  is  assumed  since  it  can  be  converted  into 
3-ohloro  pyridene.  Its  melting  point  is  187° • 


^eriohte  V.  37,  p.  3829 


t 


. 


* 


7 


II 

Reactions 

It  is  supposed  that  acetoaoetlc  ester  condenses  in  the  presence  of 
snlfnrio  acid  in  the  following  manner:  Two  molecules  of  the  ester 

condense  to  isodehydroaoetic  ester*  Part  of  the  latter  is  then  hy- 
drolized  hy  sulfuric  acid  to  form  isodehydroaoetic  acid*  A mole- 
cule of  the  latter  then  reacts  with  a molecule  of  the  ester  to  form 
an  ether  of  the  acid  and  ester  which  is  the  first  condensation 
product*  The  reaction  is  carried  out  in  the  following  manner* 


C — C-OHg 

chs-c; 

CH  —CO 


H2304 


+ Hg30, 


I 

> JS 

CH„-  C v 


C00C2H5 


:C -CH« 

:o^ 


CH  — CO 


COOH 

I 


C2H6H304+CH3-C^ 


C = C-CHg 


CH  — CO 


cooc2h5 

i 

C = C-CHcr 
CHg“  CN  > 3 

N CH  — CO 


-f- 


COOH 

) 


CHg-  CN 


= C-CHc 
✓0  1 
CH  —CO 


C2H50H 


C00C2Hg 


CHS-C, 


.CH, 


'CH  — C-O-C^Hr 

d 26 


CH 


-N 


HO-C  — C 


C-CH, 


CH3  COOfCgHg)  H 


:hso. 


The  latter  is  the  first  condensation  product* 


-• 


- 


‘ 


8 


It  further  loses  a molecule  of  alcohol  and  breaks  up  into  a molecule 
of  the  Add  and  one  of  the  ester*  This  breaking  up  is  the  reverse 
of  its  formation*  It  occurs  when  the  potash  is  added  to  the  soluticn 
of  the  condensation  product  in  ether  and  ohloroform* 


0 

C 


-(HO) 


HO  C = 0 


CH 

-c-ch3 


ch3  cooh 


COOCgHg 


CHrT  c: 


CH-CO 

+ 


COOH 

I 

,0  = 


CH3  < 

CH  — CO 


CxCHS 

xo  3 


+ 


c2h5oh 


9 


III 

EXPERIMENTAL  WORK 

* 

A.  Preparation  of  the  aoid  and  ester* 

The  Sulfuric  Aoid  Method 

The  method  used  was  slightly  different  from  that  given 
above  in  the  literature*  The  first  condensation  product  was  fil- 
tered as  above  and  the  filtrate  was  extracted  with  the  ether- 
chloroform  mixture  to  recover  any  of  the  product  that  was  dis- 
solved in  it*  After  the  layer  containing  the  potassium  salt  of 
the  aoid  had  been  separated  from  the  ether-chloroform  layer 
containing  the  ester,  the  latter  was  dried  over  calcium  chlorige 
and  the  solvent  boiled  off*  The  remainder  was  distilled  under 
diminished  pressure*  The  first  thing  that  came  over  was  a little 
unchanged  ester*  Then  came  a trace  of  mesityn  lactone  and  fol- 
lowing this  the  ester  of  isodehydroacetio  acid*  It  comes  off  at 
200°  C*  at  50  mm*  pressure* 

The  acid  is  recovered  by  neutralizing  the  potash  solution 
with  hydrochloric  acid  (dilute)  and  filtering  the  precipitate* 

It  is  reorystallized  by  throwing  it  out  of  ether  with  ligroin. 

In  all  the  methods  that  were  tried  the  first  condensation 
product  was  not  allowed  to  stand  twenty  four  hours  after  precip- 
itation and  before  filtration,  as  Hantzsch  did1* 

Preparation  A*-  The  above  method  was  used  except  that  the 
mixture  of  aoetoacetic  ester  and  sulfuric  acid  was  only  allowed 
to  stand  for  four  hours  at  a constant  temperature  of  35°  C*  The 
yield  was  17  g*  of  the  ester  coming  over  at  190-195°  C.  The 

acid  was  not  worked  up* ^ This  work,  p*3 


10 

Preparation  Bi-  The  same  method  as  above  was  used  except  that 
the  mixture  w%s  allowed  to  stand  for  fourteen  days  at  room  temper- 
ature* 

Yield:-  20  grams  of  the  ester  at  190-195°  at  40  mm*  pressure* 

7 grains  of  the  pure  acid.  Melting  point  149° 

Preparation  C:-  Same  method  as  in  B 
Yield:?  grams  of  the  ester  at  190°  at  40  mm*  pressure* 

The  acid  was  not  worked  up* 

Preparation  Si-  Same  method  as  in  B* 

Yield:-  10  grams  of  the  ester  at  198°  at  50  urn*  pressure* 

18  grams  of  the  acid*  Melting  point  1480 

Preparation  Gi-  Same  method  as  in  B* 

Yield:-  10  grams  of  the  ester  at  195°  and  40  mm*  pressure* 

The  aoid  was  not  worked  up. 

In  this  preparation  was  allowed  to  stand  for  twenty  four 
hours  to  discover  whether  that  would  increase  the  yield*  It  did 
not  do  so* 

Preparations  I,  and  J:-  Same  method  as  in  G* 

Yield  of  each:-  10  grams  of  the  ester. 

15g*  of  the  acid* 


11 


The  Hydrochloric  Acid  Method 

The  method  of  preparation  has  already  been  described  on  page 
3 of  the  thesis.  It  was  followed  exactly  as  given. 

Preparation  D:-  100  grams  of  aoetoacetio  ester  were  satur- 

ated with  dry  hydrogen  chloride  at  the  temperature  of  ice.  The 
solution  turned  brown  after  the  hydrogen  chloride  had  been  pass- 
ing into  it  for  a short  time.  It  was  allowed  to  stand  at  the 
temperature  of  ice  for  a month  and  was  then  fraotioned.  In  this 
method  there  was  none  of  the  acid  formed.  The  yield  of  ester, 
distilling  at  195°  at  43  mm.  pressure,  was  43  grams.  30  grams 
of  an  unknown  substance  came  over  at  50°  and  at  80  mm.  pressure. 
This  unknown  was  later  fraotioned  at  atmospheric  pressure  with 
the  following  results:  There  were  two  fractions,  one  coming  off 
at  87-94°,  and  the  other  at  240°.  There  was  only  a small  amount  c£ 
the  latter  and  it  was  evidently  isodehydroacetic  ester  from 
its  smell  and  boiling  point.  The  first  fraction  precipitated  the 
silver  chloride  immediately  on  a test  wit  h silver  nitrate, 
this  showed  that  the  chlorine  present  wa3  present  in  an  inorganic 
compound.  Since  the  only  things  possible  were  water,  alcohol, 
and  hydrochloric  acid  it  was  assumed  that  the  unknown  was  a mixture 
of  these  three  constituents  with  a very  little  aoetoacetio  ester. 

Preparation  F:-  The  same  method  was  used  as  above. 

Yield:-  30  grams  of  ester. 

30  fcrams  of  mesityn  lactone. 

This  disproves  Hembd’s  statement^  that  there  is  no  mesityn 
1 Hembd,  Thesis  at  Kiel,  Ger.  1914. 


I 


12 

laoton®  formed  by  this  method* 

B*  Chlorination  of  the  ester* 

The  first  method  to  be  tried  was  the  chlorination  of  the 
ester  by  the  reaction  on  it  of  chlorine  in  a carbon  tetrachlor- 
ide solution*  The  chlorine  solution  was  prepared  by  allowing 
chlorine  to  pass  thru  carbon  tetrachloride*  When  the  solution 
had  turned  a distinot  yellow  it  was  standardized  against  so- 
dium thiosulfate , using  starch  and  potassium  iodide  as  indicator* 
The  calculated  amount  of  solution  containing  the  right  amount  of 
chlorine  to  react  with  5 grams  o£  the  ester  was  then  added  to  the 
ester  in  carbon  tetrachloride  and  was  then  allowed  to  stand  in 
the  sunlight  till  there  was  no  more  free  chlorine  present*  This 
determined  by  the  use  of  starch-  potassium  iodide  paper* 

According  to  the  literature^-  the  chlorinated  ester  is  crys- 
talline* When  there  was  no  more  free  chlorine  present  the  solvent 
was  evaporated*  The  residue,  instead  of  being  crystalline,  was 
an  oil*  Cooling,  scratching  the  sides  of  the  glass,  and  other 
methods  were  tried  to  make  it  crystallize,  but  to  no  avail* 

Sulfuryl  chloride  as  the  chlorinating  agent  was  then  tried* 
The  sulfuryl  chloride  at  0°  was  added  to  the  ester  at  0°  in  a 
solution  of  dry  ether*  It  was  allowed  to  stand  at  this  temper- 

1 Annales  de  Chimie  Y*  24,  Ser*  6,'  p*  98* 


. 

. 


- 


, 

- 


T 


. 

- 

> 

* “ < •<  t 

n 

13 

attire  till  all  bubbling  had  ceased*  The  solution  was  allowed  to 
stand  at  room  temperature  over  night  and  the  ether  then  distilled 
off.  The  result  was  an  oil,  and  not  the  crystals  that  were  want- 
ed* This  oil  was  distilled  under  diminished  pressure*  All  of 
the  liquid  came  over  at  8 mm.  pressure  and  146°  C.  This  is  the 
temperature  where  the  * pure  ester  boils  at  that  pressure.  The 
distillate  was  tested  for  chlorine  with  a copper  wire  and  the 
result  was  negative.  It  is  therefore  probable  that  the  result 
was  the  unchanged  ester  and  that  no  chlorination  had  taken  place* 

To  determine  whether  the  l^ok  of  chlorination  might  be  due 
to  impure  sulfuryl  chloride^  the  latter  was  distilled  twice 
and  the  method  tried  again  with  no  better  results* 

An  attempt  was  then  made  to  chlorinate  the  acid  according  to 
the  method  of  Oppenheim  and  Precht  given  above^-*  It  was  thought 
that  if  it  were  possible  to  chlorinatethe  acid,  this  chlor  acid 
might  be  then  esterified  and  the  chlor  ester  obtained  ih  that  way. 

Following  the  above  mentioned  method  a mixture  of  the  acid 
and  chlorine  in  carbon  tetrachloride  wa3  allowed  to  stand  for  half 
an  hour.  The  solvent  was  then  distilled  off  and  the  resulting 
crystals  purified  by  throwing  them  out  of  chloroform  with  lig- 
roin.  The  melting  point  (137°)  of  these  crystals  disclosed, 
however,  that  the  acid  had  remained  unchanged.  Mixed  melting 

1 This  work,  p.  5* 


, 


/ . ; 


* 


A 


. . 

' 


, 


* n 


, 


14 

point  with  the  pure  acid— 138°  C.  This  method  was  then  a fail- 
ure. 

The  aoid,  however,  was  chlorinate. by  a modification  of  the 
above  method.  Instead  of  allowing  the  mixture  of  the  acid  and  chi 
orine  to  stand  for  only  a half  hour  it  w^s  allowed  to  stand  for  a 
week  in  sunlight.  A small  amount  of  iodine  was  present  to  catal- 
yze the  reaction.  After  a week  the  solvent  was  evaporated  off 
and  the  resulting  crystals  melted  at  94° • It  was  there- 
fore the  chlorinated  acid.  This  compound  is  soluble  in  alcohol 
and  water. 

An  esterification  of  the  acid  was  tried  using  its  silver 
salt  and  ethyl  iodide.  The  silver  salt  was  suspended  in  ether 
and  the  ethyl  iodide  added.  The  mixture  was  refluxed  for  eight 
hours  and  the  solvent  evaporated.  Only  a very  small  trace  of  the 
acid  had  been  esterified. 


. 


15 


IV 

SUMMARY 

In  doing  this  work  the  original  intention  had  been  to  chlor- 
inate the  ester  and  to  determine  the  point  in  the  ring  where  the 
chlorine  entered.  Owing,  however,  to  the  inability  to  obtain  the 
chlorinated  ester,  the  above  object  was  not  accomplished. 

There  were,  however,  some  facts  discovered  that  are  worthy  of 
note. 

It  was  discovered  that  it  is  not  necessary,  in  the  preparatiaa 
of  the  ester  by  the  sulfuric  acid  method,  to  allow  the  mixture  of 
sulfuric  acid  and  acetoacetio  ester  to  stand  for  fourteen  days. 
Almost  as  good  yields  are  obtained  by  allowing  this  mixture  to 
stand  four  hours  at  a temperature  of  35-40°  C. 

Allowing  the  first  condensation  product  to  stand  twenty  four 
hours  after  precipitation  is  unnecessary  and  does  not  increase  the 
yield. 

Contrary  to  Hembd's  statements,  mesityn  lactone  is  formed  in 
the  hydroohlorio  acid  method  of  preparation  of  the  ester. 

To  chlorinate,  the  acid  must  be  allowed  to  stand  with  a chlor- 
ine solution  for  a week  in  sunlight  and  in  the  presence  of  iodine. 


